It has been reported that children with classical phenylketonuria (PKU) have reduced levels of arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) in plasma and membrane phospholipids compared to controls and may therefore require supplementation. However, it is not established that these changes are specific for PKU. They may as well be attributed to the specific composition of a largely vegetarian diet used for dietary PKU treatment. We therefore investigated the fatty acid composition of plasma phospholipids (PL), plasma cholesterol esters (CE), red blood cell phosphatidylcholine (PC), and red blood cell phosphatidylethanolamine (PE) in two groups of PKU patients including 8 children between 1 and 6 years (group A), 9 adolescents between 11 and 18 years (group B), and 20 age-matched healthy controls. Group A had good dietary control (median plasma phenylalanine 272 mumol/L during the last 6 months before phospholipid analysis) while median phenylalanine in group B was 714 mumol/L (p < 0.001). When compared to age-matched controls, group A showed significantly lower DHA levels in PE (4.21 vs 5.85 weight% (wt%), p < 0.01), in PC (1.02 vs 1.25 wt%, p < 0.05) and in CE (0.25 vs 0.54 wt%, p < 0.05). There was no significant difference of DHA between group B and controls. AA levels were similar in phospholipids of all groups. We conclude that reduced levels of long-chain polyunsaturated fatty acids in PKU patients occur only in those patients with strict dietary therapy with respect to n-3 fatty acids, most probably caused by reduced intake of n-3 fatty acids.

Development of hyperinsulinemia was investigated which appeared late in the obese state in rats postnatally treated with L-glutamate. Insulin concentrations were estimated in the blood plasma of the caval and portal vein, and morphometric and immunohistochemical measurements of cells in the islets of Langerhans were performed, and also glucose tolerance tests. Not earlier than at 3 months hyperinsulinemia is shown in glutamate obese rats (GOR) in the peripheral blood plasma. Also in the portal blood plasma the insulin concentration is higher (167%) in GOR relative to controls. The insulin concentrations in the portal vein rise further in both animal groups whereas insulin concentration in the peripheral blood remains at the different levels in both animal groups. Impaired glucose tolerance was observed for GOR only. Islets of Langerhans in the Pancreas show enlargement and increased proliferation of B-cells in GOR. In contrast the number of D-cells is diminished. The hyperplasia of islets differs remarkably to hypoplasia of other organs in GOR. We conclude that the peripheral hyperinsulinemia is caused by a permanent hypersecretion of insulin.

Zusammenfassung:In den vergangenen Jahren hat die Messung von T-cell receptor excision circles (TRECs) zum Nachweis von schweren kombinierten T-zellulären Immundefekten (SCID) Einzug in das reguläre Neugeborenenscreening gehalten. Mit der diagnostischen Erweiterung hin zu kappa-deleting recombination excision circles (KRECs) ist dies nun auch für schwere B-zelluläre Immundefekte (primäre Agammaglobulinämien) mög-lich. Hierbei müssen molekulare Technologien in die Screeninglabore eingeführt werden, die hohe Ansprü-che an die Leistungsfähigkeit, das Auflösungsverhalten und die internationale Vergleichbarkeit der Methoden zur Messung von TRECs und KRECs stellen. Angesichts der klinischen Heterogenität der identifizierten Neugeborenen und der diagnostischen Herausforderungen in diesem Altersabschnitt sind zielführende Strategien für das Screening, Tracking und Follow-up erforderlich. In diesem Beitrag diskutieren wir die Möglichkeiten und das Zusammenwirken diagnostischer Verfahren zur zeitnahen Bestätigungsdiagnostik und therapeutischen Klassifikation von Neugeborenen mit schweren angeborenen Immundefekten.Schlüsselwörter: Lymphopenie; Neugeborenenscreening; primäre Immundefekte; SCID; XLA.Abstract: Primary immunodeficiencies such as severe combined immunodeficiency and X-linked agammaglobulinemia (Bruton's disease) are some of the latest additions to population-scale newborn screening campaigns. To identify these diseases at the neonatal stage, molecular technology to detect T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) has finally entered newborn screening laboratories, posing considerable demands towards resolution performance and comparability of the TREC and KREC assays used. Moreover, the heterogeneity of patients positively screened by these assays, and the diagnostic challenges in neonates, require comprehensive strategies for screening, tracking and follow-up. In this article, we discuss diagnostic possibilities and render the frame for rapid confirmation and therapeutic classification of neonates with severe primary immunodeficiencies originating from newborn screening programs.